New Methods for Characterizing the Complex Neural Circuitry of the Adult Drosophila Brain

141 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2007.Recently improved genetic mosaic methods permit unprecedented resolution for study of neural circuitry formation in Drosophila melanogaster. This study utilizes new mosaic methods to investigate conserved mechanisms that underlie the development of adult-specific neurons. In addition to providing several novel insights about the genetics of neural circuitry development, this study also provides a framework for increased resolution in examination of lineage and morphology in the Drosophila brain. First, mosaic analysis with a repressible cell marker (MARCM) reveals stereotyped lineage and morphogenesis in the ellipsoid body (EB), a center of locomotor regulation, resembling development of the mushroom bodies (MB's), sites involved heavily in olfactory learning. In addition, EB neuron birth and axon development are widely separated in time making them ideal model neurons for further studies. Second, comparative genetic mosaic analysis of EB and dorsal cluster (DC) neurons suggests that TGF-beta signaling is widely required for maturation and morphogenesis of post-mitotic adult-specific neurons. Third, combined application of MARCM with a newly developed technique, called "Flip-out" MARCM, reveals that the Drosophila Down syndrome cell adhesion molecule (Dscam) is required for suppressing ectopic bifurcation MB axons and for promoting divergent guidance of growth cones. Knockout of Dscam in EB neurons reveals a general role in formation and guidance of axonal branches. Finally, combining mosaic methods to study both cellular genetic requirements and phenotypes suggest a non-autonomous requirement for the atypical receptor tyrosine kinase (RTK), Linotte/Derailed (Lio/Drl), in patterning MB axon lobe architecture. In the development of MB circuitry, Lio/Drl may act to counter Wnt5 signaling, which appears to be generally required for axon extension across the brain midline.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD